9 results on '"Solakov, Panayot"'
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2. ACTIVE THERAPEUTIC IMMUNIZATION WITH TNF-KINOID IN RHEUMATOID ARTHRITIS PATIENTS WITH SECONDARY RESISTANCE TO TNFα ANTAGONISTS IS SAFE AND IMMUNOGENIC
- Author
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Durez, Patrick, Miranda, Pedro, Toncheva, Antoaneta, Berman, Alberto, Rillo, Oscar Luis, Boutsen, Yves, Kehler, Tatjana, Mociran, Eugenia, Soto, Saez Lian, Fautrel, Bruno, Mariette, Xavier, Solakov, Panayot, Lucero, Eleonora, Vlak, Tonko, Grazio, Simeon, Maštrović, Ksenija, Chirieac, Rodica, and Boissier, Marie- Christophe
- Subjects
rheumatoid arthritis, TNF alfa - Abstract
Background: Blocking TNF alpha (TNFα) with monoclonal antibodies (mAbs) has been successful in the treatment of rheumatoid arthritis. However primary and secondary resistances are frequent and impose treatment changes. Active immunization with a TNF-Kinoid that safely induces self polyclonal anti-TNFα antibodies (Abs) could be an alternative to anti-TNFα mAbs Objectives: We evaluated the immunogenicity and safety of TNF-K in patients with rheumatoid arthritis and secondary resistance to TNF blockers. Methods: TNFα-Kinoid (TNF-K, Neovacs SA, Paris, France) is an im- munotherapeutic composed of recombinant human TNFα conjugated to KLH, inactivated and adjuvanted with ISA-51 emulsion. 40 patients with active rheumatoid arthritis (DAS28≥3.2) with history of positive clinical response to TNF- blockers followed by secondary failure (35% IFX, 30% ADA, 42.5% ETA) were enrolled in a double-blind, placebo-controlled, phase 2 study to evaluate three different intramuscular doses of TNF-K (90, 180, 360 mcg) and two immunization schedules (D0 and 28 or D0, 7 and 28). Immune responses were evaluated through titration of anti-TNFα and anti-KLH Abs. Clinical response was evaluated by the ACR and EULAR core set response. Results: No related serious adverse event has been reported. Few minor transient local and systemic reactions have been recorded following immu- nization. Anti-TNFα Abs were induced in 50%, 75% and 91% of patients at 90 mcg, 180 mcg and 360 mcg, respectively. 100% of patients with three injections of 180 or 360 mcg had immunogenic response against 67% in two injections groups. Among the 21 patients who developed anti-TNF Abs, 48% present a moderate to good response according to EULAR score as opposed to only 31% of the 16 patients without Abs. A mean decrease of -14% of the C reactive protein level is measured in patients with Abs while in patients without Abs, the mean CRP level increased by 5%The mean decrease of the DAS28 score is -0.8 points in patients with Abs while it is only -0.5 in patients without Abs. Conclusions: Active immunization with TNFα kinoid to induce a polyclonal, self-anti-TNFα antibody response is safe and immunogenic. A clinical and biological response were observed in some patients included in this preliminary phase 2 study and further studies are needed to confirm this new approach in RA.
- Published
- 2013
3. Active Immunization with TNF-Kinoid in Rheumatoid Arthritis Patients with Secondary Resistance to Tumor Necrosis Factor-Alpha Antagonists Is Safe and Immunogenic
- Author
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Durez, Patrick, Miranda, Pedro, Toncheva, Antoaneta, Berman, Alberto, Rillo, Oscar Luis, Boutsen, Yves, Kehler, Tatjana, Mociran, Eugenia, Soto, Saez Lian, Fautrel, Bruno, Mariette, Xavier, Solakov, Panayot, Lucero, Eleonora, Vlak, Tonko, Grazio, Simeon, Maštrović, Ksenija, Chirieac, Rodica, and Boissier, Marie-Christophe
- Subjects
Rheumatoid arthritis – Anti-TNF therapy - Abstract
Blocking TNF alpha (TNFα) with monoclonal antibodies (mAbs) has been successful in the treatment of rheumatoid arthritis. However primary and secondary resistances are frequent and impose treatment changes. Active immunization with a TNF-Kinoid that safely induces self polyclonal anti-TNFα antibodies (Abs) could be an alternative to anti-TNFα mAbs. We evaluated the immunogenicity and safety of TNF-K in patients with rheumatoid arthritis and secondary resistance to TNF blockers. TNFα- Kinoid (TNF-K, Neovacs SA, Paris, France) is an immunotherapeutic composed of recombinant human TNFα conjugated to KLH, inactivated and adjuvanted with ISA-51 emulsion. 40 patients with active rheumatoid arthritis (DAS28≥3.2) with history of positive clinical response to TNF-blockers followed by secondary failure (35% IFX, 30% ADA, 42.5% ETA) were enrolled in a double-blind, placebo- controlled, phase 2 study to evaluate three different intramuscular doses of TNF-K (90, 180, 360 mcg) and two immunization schedules (D0 and 28 or D0, 7 and 28). Immune responses were evaluated through titration of anti-TNFα and anti-KLH Abs. Clinical response was evaluated by the ACR and EULAR core set response. No related serious adverse event has been reported. Few minor transient local and systemic reactions have been recorded following immunization. Anti-TNFα Abs were induced in 50%, 75% and 91% of patients at 90 mcg, 180 mcg and 360 mcg, respectively. 100% of patients with three injections of 180 or 360 mcg had immunogenic response against 67% in two injections groups. Among the 21 patients who developed anti-TNF Abs, 48% present a moderate to good response according to EULAR score as opposed to only 31% of the 16 patients without Abs. A mean decrease of -14% of the C reactive protein level is measured in patients with Abs while in patients without Abs, the mean CRP level increased by 5%The mean decrease of the DAS28 score is -0.8 points in patients with Abs while it is only -0.5 in patients without Abs. Active immunization with TNFα kinoid to induce a polyclonal, self-anti-TNFα antibody response is safe and immunogenic. A clinical and biological response were observed in some patients included in this preliminary phase 2 study and further studies are needed to confirm this new approach in RA. Disclosure of Interest: P. Durez: None Declared, P. Miranda: None Declared, A. Toncheva: None Declared, A. Berman: None Declared, O. L. Rillo: None Declared, Y. Boutsen: None Declared, T. Kehler: None Declared, E. Mociran: None Declared, L. Soto Saez: None Declared, B. Fautrel: None Declared, X. Mariette: None. Declared, P. Sokalov: None Declared, E. Lucero: None Declared, T. Vlak: None Declared, S. Grazio: None Declared, K. Mastrovic: None Declared, R. Chirieac: None Declared, G. Grouard-Vogel Employee of: Neovacs, O. Dhellin Employee of: Neovacs, S. Ouary Employee of: Neovacs, B. Fanget Employee of: Neovacs, P. Vandepapelière Employee of: Neovacs, M.-C. Boissier Consultant for: Neovacs
- Published
- 2012
4. Adherence to Bisphosphonate Therapy in Postmenopausal Osteoporotic Women
- Author
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Kuzmanova, Stefka, primary, Solakov, Panayot, additional, and Geneva-Popova, Mariela, additional
- Published
- 2011
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5. Active Immunization with TNF-Kinoid in Rheumatoid Arthritis Patients with Secondary Resistance to Tumor Necrosis Factor-Alpha Antagonists Is Safe and Immunogenic
- Author
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Durez, Patrick, Miranda, Pedro, Toncheva, Antoaneta, Berman, Alberto, Rillo, Oscar L., Boutsen, Yves, Kehler, Tatjana, Mociran, Eugenia, Soto Saez, Lian, Fautrel, Bruno, Mariette, Xavier, Solakov, Panayot, Lucero, Eleonora, Tonko Vlak, Grazio, Simeon, Mastrovic, Ksenija, Chiriac, Rodica, Grouard-Vogel, Geraldine, Dhellin, Olivier, Ouary, Stephane, Vandepapeliere, Pierre, and Boissier, Marie-Christophe
6. Minor and major complications of arthroscopic synovectomy of the knee joint performed by rheumatologist.
- Author
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Kuzmanova SI, Atanassov AN, Andreev SA, and Solakov PT
- Subjects
- Arthritis, Rheumatoid complications, Arthritis, Rheumatoid physiopathology, Female, Humans, Knee Joint physiopathology, Male, Middle Aged, Prospective Studies, Arthritis, Rheumatoid surgery, Arthroscopy adverse effects, Knee Joint surgery, Postoperative Complications, Rheumatology statistics & numerical data, Synovectomy
- Abstract
Unlabelled: The aim of the study was to analyze the type and incidence of major and minor complications resulting from arthroscopy with arthroscopic synovectomy of the knee joint performed by rheumatologist in different rheumatological diseases., Methods: In a prospective study the incidence of complications in arthroscopic subtotal synovectomy with subsequent tidal flow lavage was analyzed in 201 rheumatic patients. The arthroscopic synovectomies were performed by one team of rheumatologists in the operation room of the University Clinic of Rheumatology in the town of Plovdiv for a period of 8-9 years., Results: The major complications related to the arthroscopic synovectomy included septic arthritis (0.5%) and rupture of the joint capsule with edema of the thigh and leg (1.5%). The minor postarthroscopic complications were infection of the operative skin incision (2.0%), hemarthrosis (3.5%), severe postoperative pain (1.5%) and gout relapse (0.5%). Complete recovery was achieved after complications were treated and the result of the synovectomy was not compromised., Conclusion: Arthroscopic synovectomy of the knee joint performed by rheumatologist in in-patients involves low risk of complications among which minor operative and postoperative ones are prevalent. These do not compromise near and late results of the arthroscopic synovectomy.
- Published
- 2003
7. Serologic markers of early rheumatoid arthritis.
- Author
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Staikova ND, Kuzmanova SI, and Solakov PT
- Subjects
- Arthritis, Rheumatoid immunology, Humans, Prognosis, Arthritis, Rheumatoid blood, Arthritis, Rheumatoid diagnosis, Autoantibodies blood, Biomarkers blood, Peptides, Cyclic immunology
- Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects symmetrically multiple joints. Recent therapeutic strategy has been focusing on the symptoms of the disease and the ways to prevent its progression as early as possible. Thus, early diagnosis is crucial since early therapy with disease-modifying anti-rheumatic drugs reduces the severity of joint damage. It is the early period of the development of the disease that a specific and sensitive serologic test is needed. The RA patient sera contains a lot of antibodies. Some of them are not specific for RA occurring also in other diseases, others are highly specific and detectable only in rheumatoid arthritis. Rheumatoid factor (RF) is a very sensitive but poorly specific marker which makes it rather an unsuitable antibody for rheumatoid arthritis. RA-specific antibodies can be very useful for early diagnosis and prognosis of the disease. Among the antibodies described in recent years the most promising candidates are the autoantibodies to antigens containing one or more than one citrulline residues (cyclic citrulline peptides, CCP) - the anti-CCP antibodies. They have been shown in recent research to play an important role in the diagnosis, prognosis and therapeutic approach to patients with RA. Their high specificity, the ability to diagnose RA early in its development and distinguish it from other nonerosive type of arthritis, make the anti-CCP a key serologic marker in the future.
- Published
- 2003
8. Correlations between arthroscopic findings and synovial membrane histology in patients with rheumatoid synovitis of the knee joint.
- Author
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Kuzmanova SI, Zaprianov ZN, and Solakov PT
- Subjects
- Arthritis, Rheumatoid complications, Biopsy, Female, Humans, Knee Joint diagnostic imaging, Male, Middle Aged, Pilot Projects, Radiography, Synovitis etiology, Arthritis, Rheumatoid pathology, Arthroscopy, Knee Joint pathology, Synovial Membrane pathology, Synovitis pathology
- Abstract
Unlabelled: Correlation and agreement between the diagnostic results of arthroscopic and histological examinations of the synovial membrane in rheumatoid synovitis of the knee joint have been discussed in small number of studies with contradictory conclusions., Aim: The aim of the present study was to determine the correlation between the arthroscopic characteristics and histology of the synovial membrane in patients with rheumatoid arthritis and synovitis of the knee joint., Methods: Sixty-four arthroscopies of the knee joint with guided multiple synovial biopsies were performed in patients with rheumatoid synovitis. Biopsy samples were taken under visual control from the evidently inflamed synovia in four regions of the knee joint. Arthroscopic assessment of the rheumatoid synovitis was done according the standard system of ACR including 6 criteria. The histological assessment of the synovitis met the EULAR criteria including 6 morphological variables., Results: High positive correlation (r = +0.76) was established between the arthroscopic and histological assessment of the rheumatoid synovitis in the examined patients. High values were also found for the k coefficient for agreement (k = 0.70). The mean value of synovitis extent according to VAS was 43.16 mm and the mean value of intensity of the inflammatory process according to VAS was 54.31 mm., Conclusion: The agreement between the arthroscopic and histological diagnosis of the synovitis is in the range of high but not absolute correlation. The two methods are not contradictory and should be used concurrently in patients with chronic rheumatoid synovitis.
- Published
- 2003
9. Leflunomide in the treatment of refractory rheumatoid arthritis.
- Author
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Kuzmanova SI, Solakov PT, Batalov AZ, Staikova ND, Andreev SA, and Russafov PB
- Subjects
- Arthritis, Rheumatoid pathology, Arthritis, Rheumatoid physiopathology, Female, Health Status, Humans, Joints pathology, Joints physiopathology, Leflunomide, Male, Middle Aged, Prospective Studies, Severity of Illness Index, Surveys and Questionnaires, Treatment Outcome, Adjuvants, Immunologic therapeutic use, Arthritis, Rheumatoid drug therapy, Isoxazoles therapeutic use
- Abstract
Unlabelled: Leflunomide (LFL) is a modern immunomodulating medication belonging to the group of drugs that favourably affect the course of rheumatoid arthritis (RA). We present in this study the results of an open prospective trial on the effectiveness and side effects of LFL in clinically followed up patients with active RA refractory to other disease modifying anti-rheumatic drugs (DMARDS). At the onset of treatment with LFL the patients had at least 8 swollen and tender joints, the disease severity being assessed by both patients and physicians as over 3 cm VAS. ESR was higher than 40mm/lh. In all patients previous treatment with disease modifying drugs received for at least 3 months was insufficiently effective. It was discontinued prior to the therapy with LFL. Assessment of the therapeutic results was made at 3, 6 and 12 months after onset of LFL therapy. The following parameters were followed-up: 1) Number of tender joints, 2) Number of swollen joints, 3) Morning stiffness (min), 4) Global assessment of the patient (VAS 1-10 cm), 5) Global assessment of the physician (VAS 1-10 cm); 6) ESR - mm/lh; 7) Mean HAQ - the sum of all scores (0-3), divided by the number of the questions5; 8) SDAI index of RA activity6; 9) ACR20% and ACR50% positive therapeutic effect2., Results: 82 patients (mean age 53.9 yrs, age range 20-70, 12 males, 70 females) were studied. RA was diagnosed in 80 (97.6%); RA combined with spondyloarthritis was diagnosed in 2 patients (2.4%). The mean duration of RA was 5.1 +/- 3.4 yrs. 70 patients (85.4%) were rheumatoid factor positive. The therapeutic effect from the administration of LFL was markedly good as early as at 3 months from beginning of treatment and was sustained significantly favourable at 12 months. The therapeutic effect of LFL referring to ACR20% is high - 36% at 3 months from onset of therapy and increased to 51% at 12 months. A grave side effect - leucopenia with granulocytopenia was observed in one female patient. LFL is a novel effective disease-modifying drug used to treat refractory RA. In a short term period - 3 to 6 months, LFL leads to a significant clinical and functional improvement of the patients.
- Published
- 2003
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